Snapshots, by Alan Franciscus, Editor-in-Chief

Article:  Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the ION-1, -2, and -3 clinical trials—ZM Younossi—et. al
   Source: Hepatology 2015 Jun;61(6):1798-808. doi: 10.1002/hep.27724. Epub 2015 Mar 18.

Results and Conclusions:  In the phase 3 clinical trials of ledipasvir and sofosbuvir with and without ribavirin patient report outcomes were measured.  There was a total of 1,952 patients in the study.  Patients were treated for 8, 12 or 24 weeks. In the groups that received ledipasvir and sofosbuvir (without ribavirin) who had early viral load suppression there was improved quality of life that was maximized by the end of treatment.  In the group that received ledipasvir/sofosbuvir and ribavirin their quality of life decreased regardless of treatment duration until the end of treatment. 

The Bottom Line:  Ribavirin during treatment reduced quality of life, but achieving a cure improved quality of life for all of the groups including the groups who received ribavirin.

 

Editorial Comments:  This is a no-brainer, but we need more of these studies to show that being cured improved quality of life and improved overall survival.  I hope that insurance companies are hearing this and loosen up the restrictions.

Article:  Antigenic cooperation among intrahost HCV variants organized into a complex network of cross-immunoreactivity—P Skums
  Source: Proc Natl Acad Sci USA. 2015 May 26;112(21):6653-8.doi:10.1073/pnas.1422942112. Epub 2015 May 4.

 

Results and Conclusions:
Most people who become acutely infected with hepatitis C become chronically infected – up to 85%.  The reason there is such a high rate of chronic infection is not completely understood, but there are many theories.  The current paper presented a mathematical model to show how the virus contributes to hepatitis C chronicity. 

What is interesting is that various proteins of the hepatitis C virus seem to act together to escape the human host—that is certain proteins of the virus work together to draw off parts of the immune system cells so that other parts of the hepatitis C virus can survive and persist in the body and infect liver cells. This enables the hepatitis C virus to act as a network of parts to establish a chronic infection.   

The Bottom Line:  As with any discovery in science these findings need to be replicated.  If the exact mechanism can be understood an effective protective vaccine could be developed. 

Editorial Comment:  Isn’t science interesting?  The hepatitis C virus is a wily little bugger and endlessly fascinating.  The key would be to understand why this strategy works for some and not others.   This could lead to the development of an effective vaccine.

 

Article: Differentiation of acute from chronic hepatitis C virus infection by nonstructural 5B deep sequencing: A population-level tool for incidence estimation—V. Montoya et. al
   Source:  Hepatology Volume 61, Issue 6, pages 1842–1850, June 2015

 

Results and Conclusions:  In the current study the authors examined the viral proteins from 13 acute and 54 chronic individuals by sequencing the NS5B region of the virus.  They were able to differentiate the viral diversity between the acute and chronic infection.  The viral diversity was significantly different between acute vs. chronic infection. 

 
Editorial Comment:  This and the last issue of the HCV Advocate have discussed the difficult task of trying to diagnose an acute infection of HCV.  If this study is replicated and IF the tool is made available at a reasonable cost it could be a game changer in the way we understand how many people are acutely infected with hepatitis C.

Source:  http://hcvadvocate.org/news/newsLetter/2015/advocate0815.html#3

House Passes Two Historic VA Reform Bills

WASHINGTON, DC – Today, the House passed two pieces of VA reform legislation. The VA Accountability Act of 2015 passed with a vote of 256 – 170. The Surface Transportation and Veterans Health Care Choice Improvement Act of 2015 passed with a vote of 385 – 34. Chairman Miller released the following statement:

“I applaud my colleagues for stepping up today to address the troubling lack of accountability eroding VA’s ability to care for our veterans. The VA Accountability Act will provide the Secretary of the Department of Veterans Affairs the ability to make real reforms and bring much needed accountability to the department. Today, we stand with our veterans because the status quo has failed them and the American people for far too long.

“Just over two weeks ago, the Department of Veterans Affairs announced that because of its inability to budget, VA hospitals around the country would be shutting down in August. Today, the House passed the Surface Transportation and Veterans Health Care Choice Improvement Act of 2015 to ensure that does not happen. The bill is designed to rescue a mismanaged VA, providing the resources to keep the doors open, expanding access and choice to veterans and setting the stage to consolidate VA’s uncoordinated and wasteful non-VA care programs into the Veterans Choice Program.

“I urge the Senate to take up both these measures immediately. We cannot allow VA’s incompetence to continue to harm America’s veterans. And I sincerely ask President Obama to sign both in to law – to take the money without the accountability will only lead to continued failure.” – Rep. Jeff Miller, Chairman, House Committee on Veterans’ Affairs


Related:
Chairman Miller’s Floor Statement on The VA Accountability Act of 2015

Chairman Miller’s Floor Statement on The Surface Transportation and Veterans Health Care Choice Improvement Act of 2015

Ireland: The psychological effects of hepatitis C: 'It was a dirty and uneasy feeling and it began to haunt me'

It was in the early noughties when I first got my bloods tested. I wasn't even thinking about hepatitis C at that time, that wasn't on my radar at all. To be honest, I only got tested because a number of other people in the methadone clinic I attended at that time were getting tested. I had no idea that test would turn out to be the turning point in my life and the reality check that I needed.

At this point, my lifestyle was chaotic. This was down to my misuse of drugs and the type of life that comes with taking that path.

My issues with addiction started very early on, when I was 14. Like many others from my area at the time, peer pressure to do drugs was a big issue - like many teenagers I suffered from low self-esteem and drugs were an appealing way to 'fit in'.

Read more...

A Brief Overview: Outbreaks of Acute HCV Infections in the U. S., by Alan Franciscus, Editor-in-Chief

In this review, I will discuss the outbreaks of acute infections of hepatitis C across the United States in urban and rural centers. 

Before I start discussing this very important issue, I would like to set the stage by going over the case definition of hepatitis C (HCV) acute infection as defined by the Centers for Disease Control and Prevention (CDC): 

“Laboratory-confirmed infection with infection with acute illness of discreet onsite.  An acute illness is considered as the presence of any sign or symptom of acute viral hepatitis plus either jaundice or elevated alanine aminotransferase >400 IU/L. In 2012, the surveillance case definition was expanded to include cases with negative HCV antibody followed by positive antibody within six months.”

To me there are problems with the CDC case definition.  Regarding the first part of the definition—an estimated two-thirds of people acutely infected have few or no symptoms.  This means that they are missing the majority of people who are acutely infected with HCV.  The new case definition regarding prior antibody testing is better, but it does not accurately capture people who are new to injecting drugs or people who have never been tested for hepatitis C.  However, it is understandable how difficult it is to set the criteria to define an acute infection.   Note:  In “Snapshots” this month there is a recap of a study that may provide a test to identify acute cases of HCV.

In the July 2015 HCV Advocate Mid-Monthly Edition, I wrote about an article published in the Annals of Internal Medicine titled “Underascertainment of Acute Hepatitis C Virus Infections in the U.S. Surveillance System: A Case Series and Chart Review,” by S Onofrey, MPH et. al.  The authors concluded that only 1% of acute infections has been reported to the CDC based on their case definition.  Keep the 1% in mind when reading the information below. 

Massachusetts
In July 2011 I wrote about the Massachusetts outbreak of acute HCV among young people who inject drugs.  In the CDC report Massachusetts initiated a comprehensive surveillance system and identified 1,925 new cases of HCV infections among people aged 15-24 years during 2007 to 2009.  Of these cases, 1026 were confirmed new hepatitis C infections and the remaining cases were classified as probable.  It was also interesting that the new hepatitis C infections were not just confined to the major metropolitan and suburban areas of Boston, but high rates were also found in smaller cities and rural areas.  It was also reported that the incidence of new HCV infections were similar in women and men and were seen mostly among non-Hispanic whites.  In the analysis, 72% of the people reported current or past injection drug use.  Among the people who self-disclosed that they injected drugs—85% used heroin, 29% cocaine, 1% methamphetamine and 4% had used other drugs.  Some of the characteristics seen in the Massachusetts outbreaks —rural, young, mostly White using heroin—were the beginning of a trend seen throughout the country. 

Massachusetts has an extensive network of needle exchanges.  One can only imagine what the number of acute infections would be without a needle exchange network.

Wisconsin
In “Notes from the Field:  Hepatitis C Virus Infections Among Young Adults—Rural Wisconsin, 2010,” a report from the CDC issued on May 18, 2012 /61(19);358-358 a number of outbreaks in rural counties of Wisconsin were discussed.  It was reported that in 6 contiguous rural counties of Wisconsin that in persons under 30 yo that the number of HCV infections had increased from an average of 8 cases per year during 2004 – 2008 to an average of 24 cases per year during 2009 – 2010. 

The CDC investigated 25 cases during 2010 of the adults under 30 years old who resided in the 6 counties.  Of these patients 7 had jaundice (a rare symptom of acute HCV).  All 21 had positive antibody tests.  Twenty-one had positive EIA with signal-to-cutoff ratio or had a test to confirm the presence of HCV RNA (viral load test).  Additionally, seventeen patients were interviewed. Of the patients who were interviewed (17 pts) 94% had either injected drugs, snorted drugs or both.

The age group that had the highest prevalence was those 20-29 yo, which is a national trend of people who inject drugs in rural areas. No information about the sex of the patients was given in the report.  

Ohio
In Ohio, the number of confirmed cases of acute cases HCV was 112 in 2013 and 105 in 2014.  The demographics are similar to the demographics in other outbreaks across the U.S. —mostly white, equally divided among gender and many of the acute cases occurred in rural settings. 

Indiana
The May 1st issue of the Morbidity and Mortality Weekly Report (MMWR), contained “Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorphone—Indiana, 2015, by C Conrad,” which describes a recent outbreak of HIV and HCV in a rural community of Indiana.  On January 23, 2015 the Indiana State Department of Health began an investigation on an outbreak of HIV after 11 cases were reported and confirmed.  Although little attention was given to HCV there was a confirmed HIV/HCV coinfection rate of 84.4%!  All of the people who injected drugs reported crushing, dissolving and injecting oxymorphone tablets as well using other drugs including methamphetamine and heroin.  The total number of people who tested positive for HIV was 135.  The community in rural southeastern Indiana had a population of 4,200.  The age range was 18 to 57 yo (median 35 yo), 54.8% were male.  

The response to the outbreak is best summed up by a statement in the MMWR: “A public health emergency was declared on March 26 by executive order.  The response has included a public education campaign, establishment of an incident command center and a community outreach center, short-term authorization of syringe exchange, and support of comprehensive medical care including HIV and hepatitis C virus care and treatment as well as substance abuse counseling and treatment.”  Hopefully, the ‘short-term’ will be changed to ‘permanent.’

Maine
On July 6, 2015 the Portland Press Herald reported on a surge of hepatitis C cases: during 2013 to 2014 the incidence of acute HCV increased from 9 to 31 cases and there were 14 cases in the first 6 months of 2015.   The users who were interviewed stated that they had started with opiates like Oxycontin and switched to heroin. This is a recurring theme.   Maine has 5 needle exchange programs.  

Kentucky, Tennessee, Virginia and West Virginia (2006-2012)
The CDC released an MMWR report on May 8, 2015 titled “Increases in Hepatitis C Virus Infection Related to Injection Drug Use Among Persons Aged ≤ 30 Years –Kentucky, Tennessee, Virginia, and West Virginia, 2006—2012,” by J E Zibbell and Colleagues detailing the outbreaks in the Appalachia region of the U.S.   

A total of 1,377 cases of acute HCV were reported to the CDC during the period 2006-2012 from Kentucky, Tennessee, Virginia and West Virginia.  There were 1,374 cases reported where the age was available—616 (44.8%) were ≤ 30 yo (median age 25 yo—range in urban and non-urban 6-30 yo).

The number of persons who were non-Hispanic whites in non urban settings was 247 (78.4%); males, 156 (49.5%); in urban counties, 249 (82.7%) cases were non-Hispanic whites, and 155 (51.5%) were males. See Figure 1 below.   

Comments:  The trend of acute HCV outbreaks that started in Massachusetts is continuing across the United States.  This includes more adolescents and young adults injecting, infecting as many women as men and in rural more than urban settings.   What is even more disturbing is the reaction of the local and state governments—needle exchange being started post-outbreak rather than establishing needle exchange as prevention.  Almost every outbreak has resulted in the establishment of a needle exchange program after an outbreak.  If needle exchange programs had been in place before an outbreak many of the HIV and HCV infections could have been prevented. 

Figure 1

Figure 1.  Incidence of acute hepatitis C among persons ≤ 30, by urbanicity and year –Kentucky, Virginia, Tennessee, and West Virginia, 2006 –2012.

Source:  http://hcvadvocate.org/news/newsLetter/2015/advocate0815.html#1

Highway Bill Gives $500 Million to Veterans’ Hepatitis Drugs

The U.S. Department of Veterans Affairs was authorized to spend as much as $500 million for hepatitis C treatments through Oct. 1 as part of the emergency highway funding bill signed into law on Friday.

The spending could provide a short-term sales boost for Gilead Sciences Inc., which makes the hepatitis C treatments Harvoni and Sovaldi, and for AbbVie Inc., which makes a similar drug, Viekira Pak. Gilead sold $4.9 billion of its hepatitis C pills in the second quarter, while AbbVie sold $385 million of its treatment in the same period.

While the drugs provide a cure for the disease, which can cause liver damage to the point of needing a transplant, their prices have attracted a firestorm of criticism from politicians and insurers. List prices for the treatments are more than $83,000 for a 12-week course.

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Hepatitis C numbers up in Maine, Androscoggin County

Hepatitis C numbers are up in Maine, with Androscoggin County seeing some of the highest rates of acute cases in the state.

Experts say there are a variety of reasons for the increase, including a spike in heroin use — the hepatitis C virus is transmitted by blood and shared needles commonly spread it — and a new, dramatically more effective treatment that's made patients more willing to be tested.

"We are seeing people coming out of the woodwork to seek treatment for hepatitis C," Imad Durra, infectious disease specialist with Central Maine Infectious Diseases in Lewiston, said.

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HealthWise: Hepatitis C and Nonalcoholic Fatty Liver Disease —Lucinda K. Porter, RN

Recently I saw a post from a patient who was cured of hepatitis C, only to find out that he had fatty liver disease. I felt bad for him, since now he has another liver disease to contend with, but then I thought it over. Fatty liver disease can be fixed, and the cure may help more than his liver—it may help him live longer and feel better.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease that generally occurs in overweight patients. It may also occur in patients whose weight is normal, but because of prior excess weight, they developed insulin resistance, diabetes, or fat in the liver area, called visceral fat. NAFLD may also arise in people who eat a high fat, low-nutrition diet.

NAFLD is the most common liver disease, and it is increasing in prevalence and severity. Since fat impairs liver regeneration, NAFLD can lead to fibrosis and cirrhosis. NAFLD is the third most common risk factor for primary hepatocellular carcinoma. The American diet is so harmful, that children are developing NAFLD. If we keep on this course, NAFLD may overtake hepatitis C as the single most common reason for liver transplantation. Tragically, the prevalence of NAFLD is so great, that there has been a decrease in the number of viable livers that can be used for transplantation.

Hepatitis C appears to increase the risk of NAFLD. However, before blaming hepatitis C for fatty liver disease, keep in mind that the prevalence of hepatitis C in the U.S. is less than 2 percent, whereas the prevalence of NAFLD is 30 percent. This makes it hard for hepatitis C to be the sole link to NAFLD. An exception is in genotype 3, where there is clearly a higher risk for NAFLD.

As I stated, fatty liver disease can be fixed. You probably already figured out that good nutrition and maintaining a healthy weight is important, but did you know that physical activity could improve NAFLD? Exercise also improves insulin resistance as well as cardiovascular health. A few studies bear this out, but the question some of us have is, “What kind of exercise, how much, and how often?”

Let me state this in a way that I can relate to, “What is the least amount of exercise in both time and intensity that I can get away with, and still look my doctor in the eye and say I am a regular exerciser?”

In a retrospective analysis of obese middle-aged men (Hepatology April 2015), Sechang Oh and colleagues reported that moderate to vigorous physical activity had a dramatic effect. Those who engaged in ≥ 250 minutes a week of moderate to vigorous physical activity had the most improvement of NAFLD.

That is more than four hours of exercise weekly. Surprisingly, the exercise seemed to improve liver health, regardless of weight loss. Other research shows similar benefits. When it came to liver health, aerobic activity showed more improvement than resistance training.

What is moderate to vigorous physical activity?
There are various was to measure intensity. I prefer the concept of relative intensity. Using this method, people pay attention to how physical activity affects their heart rate and breathing. Intensity level is subjective. What may be intense for one person may be less intense for someone else. For instance, I don’t play tennis, but if I were to try, I would probably be huffing and puffing after the first serve. On the other hand, I do aerobic dance, and it takes me a bit of effort to raise my heart rate.

In general, if you are doing moderate-intensity activity you can talk, but not sing, during the activity. If you are engaged in vigorous-intensity activity, you will not be able to say more than a few words without pausing for a breath.

According to the Centers for Disease Control and Prevention, examples of moderate-intensity activity are:

• Walking briskly (3 miles per hour or faster, but not race-walking)
• Water aerobics
• Bicycling slower than 10 miles per hour
• Tennis (doubles)
• Ballroom dancing
• Gardening

Examples of vigorous-intensity activity are:

• Race walking, jogging, or running
• Swimming laps
• Tennis (singles)
• Aerobic dancing
• Bicycling 10 miles per hour or faster
• Jumping rope
• Heavy gardening (continuous digging or hoeing)
• Hiking uphill or with a heavy backpack

Then there is the concept of duration. Perhaps 250 minutes a week is too much for you. Before you throw in the towel, bear in mind that any exercise is better than none. I don’t care if you are walking once around the table, it is better than sitting all the time. In fact, prolonged sitting is very unhealthy.

Prolonged sitting (eight to 12+ hours per day) increases risk of developing type 2 diabetes by 90 percent. It is also associated with increased premature death from cardiovascular conditions and cancer. The World Health Organization lists physical inactivity as the fourth-leading risk factor for death for people all around the world. It ranks up there with smoking.

When I first heard this, I thought, “I am screwed.” Writers sit a lot. Yes, I exercise every day, but I also sit a lot. After I was done whining, I set about to solve my sitting problem. I bought a stand-up desk, and set a timer to remind me to walk every hour. In addition to my regular workout, I added in a longer walk after dinner. I set a goal to stand during phone calls and commercials.

There are many other benefits of adding more physical activity in to your life. Last month, I talked about hepatitis C and the value of exercise for reducing chronic pain. Exercise helped alleviate arthritic and inflammatory pain, fibromyalgia, migraine headaches and back pain. Being active improves our sleep and our moods. We live longer, and the quality of our lives is better.

If you are new to exercise, be sure to talk to your medical provider before starting. Start slow and only do what feels comfortable. Most of all, do it. Find ways to battle every excuse. Make exercise a non-negotiable part of your life. It may be hard, but it is worth it.

Lucinda K. Porter, RN, is a long-time contributor to the HCV Advocate and author of Free from Hepatitis C and Hepatitis C One Step at a Time. Her blog is http://www.lucindaporterrn.com/

Resources

• Centers for Disease Control and Prevention’s Division of Nutrition, Physical Activity, and Obesity
• Medline Plus’s Exercise and Physical Fitness

Source: http://hcvadvocate.org/news/newsLetter/2015/advocate0815.html#2